Canine Squamous Cell Carcinoma Research Articles

Correlation between malignant histological features of canine digital Squamous cell carcinoma and genetic KIT Ligand copy number variation

Correlation between malignant histological features of canine digital Squamous cell carcinoma and genetic KIT Ligand copy number variation

Investigating Cox-2 and EGFR as Biomarkers in Canine Oral Squamous Cell Carcinoma: Implications for Diagnosis and Therapy.

Oral squamous cell carcinoma (OSCC) is a common and highly aggressive dog tumor known for its local invasiveness and metastatic potential. Understanding the molecular mechanisms driving the development and progression of OSCC is crucial for improving diagnostic and therapeutic strategies. Additionally, spontaneous oral squamous cell carcinomas in dogs are an excellent model for studying human counterparts. In this study, we aimed to investigate the significance of two key molecular components, Cox-2 and EGFR, in canine OSCC. We examined 34 tumor sections from various dog breeds to assess the immunoexpression of Cox-2 and EGFR. Our findings revealed that Cox-2 was highly expressed in 70.6% of cases, while EGFR overexpression was observed in 44.1%. Cox-2 overexpression showed association with histological grade of malignancy (HGM) (p = 0.006) and EGFR with vascular invasion (p = 0.006). COX-2 and EGFR concurrent expression was associated with HGM (p = 0.002), as well as with the presence of vascular invasion (p = 0.002). These data suggest that Cox-2 and EGFR could be promising biomarkers and potential therapeutic targets, opening avenues for developing novel treatment strategies for dogs affected by OSCC. Further studies are warranted to delve deeper into these findings and translate them into clinical practice.

Upregulation of SLUG expression in canine mammary gland tumors and its prognostic significance

BackgroundSLUG (also known as snai2), which is a transcription factor in epithelial–mesenchymal transition (EMT), plays an important role in tumorigenesis. Several human studies have revealed that SLUG expression downregulates E-cadherin activity to induce metastasis and invasion of tumor cells, and its association with tumor mechanisms is under constant evaluation. In clinical veterinary medicine, one study revealed upregulated SLUG expression in canine oral squamous cell carcinoma. However, the association between canine mammary gland tumors (MGT), the most common neoplasm in intact female dogs, and SLUG has not been investigated yet. Therefore, this study aimed to evaluate the differences in SLUG expression among canine normal mammary gland tissue and MGTs using immunohistochemistry. In addition, its prognostic significance was evaluated by analyzing the correlation with the Ki-67 proliferation index and various clinicopathological features.ResultsSLUG expression increased substantially from normal mammary gland tissues to MGTs, especially showing the strongest expression in malignant MGT than in benign MGT. Negative SLUG expression was observed in mostly normal mammary gland tissues, whereas all tissues in malignant MGT showed positive SLUG expression. Furthermore, positive SLUG expression was associated with higher Ki-67 index, larger tumor size (> 3 cm), and metastasis. Kaplan–Meier survival curve analysis revealed that positive SLUG expression was significantly associated with poor overall and disease-free survival.ConclusionsThese results indicate that SLUG is upregulated in canine MGTs and positive SLUG expression is positively correlated with poor prognosis. Thus, SLUG protein can be a novel biomarker and therapeutic target for canine patients with MGT.

MicroRNA-203 inhibits migration and invasion of canine tonsillar squamous cell carcinoma cells by targeting SLUG.

Squamous cell carcinoma (SCC) occurring in the tonsils (TSCC) has a poorer prognosis than SCC occurring in other regions of the oral cavity (non-tonsillar SCC [NTSCC]) because it easily metastasizes to distant organs. This study aimed to elucidate the molecular mechanisms underlying the migration and invasion of TSCC cells in vitro. This study focused on differential microRNA (miRNA) expression using microRNA microarrays and quantitative polymerase chain reaction in canine TSCC and NTSCC tissues and cell lines. A target gene of the miRNA involved in cell migration and invasion was validated by wound healing, transwell, and luciferase assays. miR-203 expression was lower in TSCC tissues than in the normal oral mucosa and NTSCC tissues. Transfection of the miR-203 mimic resulted in the downregulation of mesenchymal marker protein expression and attenuation of cell migration and invasion in TSCC cells, but not in NTSCC cells. A dual-luciferase assay revealed that miR-203 directly targeted the mesenchymal transcription factor SLUG. SLUG overexpression enhances the migration of TSCC cells. Our study indicates that the miR-203/SLUG axis may be involved in the metastatic mechanisms of TSCC.

What is your diagnosis? Large perianal mass in a dog.

Veterinary Clinical PathologyEarly View WHAT IS YOUR DIAGNOSIS? What is your diagnosis? Large perianal mass in a dog Candice P. Chu, Candice P. Chu orcid.org/0000-0001-8543-7233 Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USASearch for more papers by this authorMary B. Nabity, Corresponding Author Mary B. Nabity [email protected] Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA Correspondence Mary B. Nabity, Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, 4467 TAMU, College Station, TX 77843-4467, USA. Email: [email protected]Search for more papers by this authorBrian F. Porter, Brian F. Porter Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USASearch for more papers by this authorAlexander Aceino, Alexander Aceino Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA Antech Diagnostics Inc, College Station, Texas, USASearch for more papers by this author Candice P. Chu, Candice P. Chu orcid.org/0000-0001-8543-7233 Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USASearch for more papers by this authorMary B. Nabity, Corresponding Author Mary B. Nabity [email protected] Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA Correspondence Mary B. Nabity, Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, 4467 TAMU, College Station, TX 77843-4467, USA. Email: [email protected]Search for more papers by this authorBrian F. Porter, Brian F. Porter Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USASearch for more papers by this authorAlexander Aceino, Alexander Aceino Department of Veterinary Pathobiology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA Antech Diagnostics Inc, College Station, Texas, USASearch for more papers by this author First published: 30 May 2023 https://doi.org/10.1111/vcp.13231Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL REFERENCES 1Williams LE, Gliatto JM, Dodge RK, et al. Carcinoma of the apocrine glands of the anal sac in dogs: 113 cases (1985–1995). J Am Vet Med Assoc. 2003; 223(6): 825- 831. 2Sakai H, Murakami M, Mishima H, et al. Cytologically atypical anal sac adenocarcinoma in a dog. Vet Clin Pathol. 2012; 41(2): 291- 294. doi:10.1111/j.1939-165X.2012.00430.x 3Nibe K, Uchida K, Itoh T, Tateyama S. A case of canine apocrine sweat gland adenoma, clear cell variant. Vet Pathol. 2005; 42(2): 215- 218. doi:10.1354/vp.42-2-215 4Gama A, Alves A, Gartner F, Schmitt F. p63: a novel Myoepithelial cell marker in canine mammary tissues. Vet Pathol. 2003; 40(4): 412- 420. doi:10.1354/vp.40-4-412 5Nagamine E, Hirayama K, Matsuda K, et al. Invasive front grading and epithelial-mesenchymal transition in canine oral and cutaneous squamous cell carcinomas. Vet Pathol. 2017; 54(5): 783- 791. doi:10.1177/0300985817707005 6Polton GA, Brearley MJ, Green LM, Scase TJ. Expression of E-cadherin in canine anal sac gland carcinoma and its association with survival. Vet Comp Oncol. 2007; 5(4): 232- 238. doi:10.1111/j.1476-5829.2007.00131.x Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

Mutations in exon 5 of the p53 gene in canine cutaneous squamous cell carcinomas

Mutations in exon 5 of the p53 gene in canine cutaneous squamous cell carcinomas

Canine squamous cell carcinoma: Electrochemotherapy association with surgery and correlation with overall survival.

Squamous cell carcinoma (SCC) is an important malignancy in dogs, due to its incidence and clinical presentation, which can be of locally aggressive single or multiple lesions with a metastatic potential. The objective of this investigation was to evaluate SCC response to treatment, anatomopathological and immunohistochemical characteristics, disease-free interval and overall survival time. 54 dogs with histopathologically diagnosed SCC were included in this study. Their mean age was 9.16 years with a range of 1-14 years. Of the 54 animals in the study, 34 (65.4%) had white skin and white fur coats. There was a significant correlation between fur coat colour and the development of tumours in areas of sun exposure (p=.001). Animals with tumours in areas of the body exposed to the sun had longer overall survival time than animals with tumours in areas not associated with sun exposure (p=.001). Surgery combined with electrochemotherapy (ECT) yielded a survival rate 32% higher than using a surgical approach alone (HR=0.32, p=.038, IC=0.11-0.94). ECT, with or without surgery, had an objective response rate of 90.9%. Local lymph node and/or distant site metastasis at diagnosis, or at some point during follow-up, occurred in 34.6% (18/52) of animals. Animals with tumours in sun exposed locations had more aggressive histopathological characteristics but had longer overall survival time. This is probably due to individualised therapeutic treatment with both surgery and ECT.

Cover Image

The cover image is based on the Short Communication Highly recurrent BRAF p.V595E mutation in canine papillary oral squa-mous cell carcinoma by Santiago Peralta et al., https://doi.org/10.1111/vco.12869.image

Canine oral squamous cell carcinoma as a spontaneous, translational model for radiation and immunology research.

Improving outcomes for oral squamous cell carcinoma (OSCC) patients has been hindered by a lack of effective predictive animal models. Spontaneously occurring canine OSCC could help fill this gap. The objective of this study was to characterize the immune landscape of canine OSCC to advance understanding of how dogs could serve as a surrogate for human OSCC. Canine OSCC contains a heterogenous tumor immune microenvironment. CD3+ T cells were the predominant tumor infiltrating immune cell population; however, there was a wide range CD3+ T cell density across samples. The most common CD3+ T cell micro-anatomical distribution was defined as "pre-existing immunity", but the remaining 20% of tumors were characterized as "immunologically ignorant" or "excluded infiltrates" patterns. When compared to normal oral mucosa, the tumor gene expression pattern suggests that canine OSCC microenvironment is highly inflamed and characterized by the presence of an anti-tumor immune response dominated by cytotoxic\effector T cells and NK cells (CD8a, GZMA, OX40, and HLA-A); however, overexpression of genes associated with effector T cell exhaustion and microenvironmental immunosuppression was also identified (PD-1, LAG3, CXCL2). Correlations between CD3+ T cell density and immune gene expression revealed key genes associated with cytotoxic anti-tumor T cell responses (GZMA, GZMB, PRF1), co-stimulation of T cells (CD27, CD28, ICOS), and other immune processes, including Type I IFN response (TNF, TNFSF10), and T cell exhaustion (CTLA4, PD-1). CD3+ T cell density in canine OSCC was significantly correlated with a cytolytic activity score (mean PRF1 and GZMA expression), suggestive of active effector CD8 T cell function. CD204+ macrophages were the second most abundant tumor infiltrating immune cell, and when comparing to normal oral mucosa, two differently expressed genes linked to tumor associated macrophages and myeloid derived suppressor cells (MDSC) were identified: CXCL2, CD70. Overexpression of CXCL2 was also identified in canine OSCC "T cell-high" tumors compared to "T cell-low" tumors. This study identified actionable immunotherapy targets which could inform future comparative oncology trials in canine OSCC: CTLA-4, PD-1, CXCL2. These data provide a good first step towards utilizing spontaneous canine OSCC as a comparative model for human OSCC radiation and immuno-oncology research.

Podoplanin promotes cell proliferation, survival, and migration of canine non-tonsillar squamous cell carcinoma.

Podoplanin (PDPN) is a prognostic factor and is involved in several mechanisms of tumor progression in human squamous cell carcinoma (SCC). Canine non-tonsillar SCC (NTSCC) is a common oral tumor in dogs and has a highly invasive characteristic. In this study, we investigated the function of PDPN in canine NTSCC. In canine NTSCC clinical samples, PDPN overexpression was observed in 80% of dogs with NTSCC, and PDPN expression was related to ki67 expression. In PDPN knocked-out canine NTSCC cells, cell proliferation, cancer stemness, and migration were suppressed. As the mechanism of PDPN-mediated cell proliferation, PDPN knocked-out induced apoptosis and G2/M cell cycle arrest in canine NTSCC cells. These findings suggest that PDPN promotes tumor malignancies and may be a novel biomarker and therapeutic target for canine NTSCC.

BUBR1 as a Prognostic Biomarker in Canine Oral Squamous Cell Carcinoma.

Chromosomal instability (CIN) plays a key role in the carcinogenesis of several human cancers and can be related to the deregulation of core components of the spindle assembly checkpoint (SAC) including BUBR1 protein kinase. These proteins have been related to tumor development and poor survival rates in human patients with oral squamous cell carcinoma (OSCC). To investigate the expression of the SAC proteins BUBR1, BUB3 and SPINDLY and also Ki-67 in canine OSCC, we performed an immunohistochemical evaluation in 60 canine OSCCs and compared them with clinical and pathological variables. BUBR1, Ki-67, BUB3 and SPINDLY protein expressions were detected in all cases and classified as with a high-expression extent score in 31 (51.7%) cases for BUBR1, 33 (58.9%) cases for BUB3 and 28 (50.9%) cases for SPINDLY. Ki-67 high expression was observed in 14 (25%) cases. An independent prognostic value for BUBR1 was found, where high BUBR1 expression was associated with lower survival (p = 0.012). These results indicate that BUBR1 expression is an independent prognostic factor in these tumors, suggesting the potential use for clinical applications as a prognostic biomarker and also as a pharmacological target in canine OSCC.

Immunohistochemical Evalution of Endoglin (CD 105) as Angiogenic Endothelial Marker of Squamous Cell Carcinoma in Dogs

Back ground: Angiogenesis is the process of using existent vascular bed to form new blood vessels. Neoangiogenesis is one of the hallmarks of cancer for tumour progression and metastasis. Microvessel density (MVD) is a powerful prognostic tool in oncology for assessing the tumour vasculature. Endoglin (CD 105) is a specific marker for activated endothelium. The present research intends to investigate the prognostic and metastatic potential of Endoglin (CD 105) and immunohistochemical expression in canine squamous cell carcinoma (SCC). Method: Totally, 15 SCC were collected from the Veterinary Clinical Complex, Tirunelveli during a one year period. The tumours were histopathologically identified as different grades. Immunohistochemically analysed with Endoglin (CD 105) and Peritumoural microvessel density and intratumourl microvessel density (PTMVD and ITMVD) were calculated using the “hot spot method”. Result: All the cases were positive for CD 105 and were strongly stained with both peritumoural and intratumoural blood vessels. Among the different types of SCC, Grade III had the highest values of microvessel density. The study concluded that different grades have different MVD values within SCC cases, thereby reflecting the behaviour of neoplasms directly. Endoglin (CD 105) is one of the best endothelial markers to determine MVD because it aids to assess the prognostic and metastatic potential of tumours and it plays a significant role in the estimation of overall survival period after surgery.

P-S6 as a Prognostic Biomarker in Canine Oral Squamous Cell Carcinoma.

Scarce information exists on the role of mTOR pathway proteins and their association to aggressiveness and prognosis of patients with canine oral cancers. We aimed to investigate the activated form of mTOR and its downstream S6 protein in canine oral squamous cell carcinoma (OSCC), and to evaluate potential associations between protein expression and clinic-pathologic variables and survival. For that we analysed p-mTOR and p-S6 protein expression by immunohistochemistry in 61 canine OSCCs. Multivariate analysis was conducted to examine their role in patients’ cancer-specific survival (CSS). p-mTOR and p-S6 expression were present in almost all cases. High-expression of p-mTOR was observed in 44 (72.1%) cases using extent score and 52 (85.2%) cases using intensity score. For p-S6, high expression was observed in 53 (86.9%) cases using extent score and in 54 (88.5%) cases using intensity score. An independent prognostic value for p-S6 extension (p = 0.027), tumour stage (p = 0.013) and treatment (p = 0.0009) was found in patients’ CSS analysis. Our data suggest that p-mTOR and p-S6 proteins are commonly expressed in canine OSCC and p-S6 expression is correlated with poor CSS in dogs with OSCC. More studies should be performed to identify possible therapeutic targets related with mTOR pathway for these patients.

A Critical Review of the risk factors associated with Canine Squamous Cell Carcinoma development

Squamous cell carcinoma (SCC) is a common neoplastic skin disease that is highly prevalent in tropical countries. As the skin has a variety of cells, overexposure to environmental factors, such as ultraviolet light, can affect this organ, resulting in malignancies, such as cutaneous SCC, hemangioma, and hemangiosarcoma. SCC arises from keratinocytes in the skin and is locally invasive with low metastatic rates, commonly affecting unpigmented skin in sites with high exposure to sunlight, such as ventral regions. SCC has a variable etiology that is not well understood. Therefore, literature review aimed to critically evaluate the risk factors involved in the SCC development.

Functional analysis of the miR-145/Fascin1 cascade in canine oral squamous cell carcinoma.

Canine oral squamous cell carcinoma (SCC) often develops in the gingiva and tonsils. The biological behavior of canine oral SCC is similar to that of human head and neck SCC (HNSCC). Inhibiting invasion and metastasis is major importance for the treatment of canine and human HNSCC. In this study, the significance of microRNA (miR)-145 and Fascin1 (FSCN1) in the invasion of canine oral SCC was explored. Canine oral SCC tissues and cell lines were used for miR-145 and FSCN1 expression analysis via real-time PCR and immunohistochemistry. Canine oral SCC cell lines were used for in vitro assays. miR-145 was downregulated while FSCN1mRNA was upregulated in canine oral SCC. Immunohistochemistry revealed that FSCN1 was upregulated in SCC when compared to normal mucosa. Transfection of canine SCC cells with miR-145 or FSCN1siRNA suppressed cell growth and attenuated cell migration as well as invasion by inhibiting the epithelial-to-mesenchymal transition. Furthermore, the promoter region of miR-145 was highly methylated in SCC cell lines and tissues. The expression profile and functions of miR-145 in canine oral SCC are similar to those in human HNSCC. Thus, canine oral SCC may represent a valuable preclinical model for human HNSCC.

VEGF Expression, Cellular Infiltration, and Intratumoral Collagen Levels after Electroporation-Based Treatment of Dogs with Cutaneous Squamous Cell Carcinoma.

Canine cutaneous squamous cell carcinoma (SCC) is the most common type of skin cancer in tropical countries and is generally associated with exposure to solar ultraviolet light. It has a low metastatic rate, and local treatments, such as electrochemotherapy (ECT), promote long-term control or even complete remission. This study aimed to evaluate pre- and post-ECT treatment expression levels of vascular endothelial growth factor (VEGF) and CD31, cellular infiltration, and intratumoral collagen levels in dogs with cutaneous SCC. A prospective nonrandomized clinical study was performed using dogs with spontaneous SCC treated with ECT. Eighteen lesions from 11 dogs were included in the study. The expression levels of VEGF and CD31; cellular infiltration; and intratumoral collagen levels, as determined by Masson’s trichrome staining, were not significantly different from pre-treatment measurements on day 21 (p > 0.05). However, among cellular infiltration, the mixed subtype was correlated with better overall survival time when compared to lymphoplasmacytic and neutrophilic infiltration (p < 0.05). In conclusion, ECT had no effect on VEGF expression, cellular infiltration, or intratumoral collagen levels in dogs with cutaneous SCC at the time of evaluation, suggesting that early and late post-ECT-treatment phases should be considered.

Comparative transcriptional profiling of canine acanthomatous ameloblastoma and homology with human ameloblastoma

Ameloblastomas are odontogenic tumors that are rare in people but have a relatively high prevalence in dogs. Because canine acanthomatous ameloblastomas (CAA) have clinicopathologic and molecular features in common with human ameloblastomas (AM), spontaneous CAA can serve as a useful translational model of disease. However, the molecular basis of CAA and how it compares to AM are incompletely understood. In this study, we compared the global genomic expression profile of CAA with AM and evaluated its dental origin by using a bulk RNA-seq approach. For these studies, healthy gingiva and canine oral squamous cell carcinoma served as controls. We found that aberrant RAS signaling, and activation of the epithelial-to-mesenchymal transition cellular program are involved in the pathogenesis of CAA, and that CAA is enriched with genes known to be upregulated in AM including those expressed during the early stages of tooth development, suggesting a high level of molecular homology. These results support the model that domestic dogs with spontaneous CAA have potential for pre-clinical assessment of targeted therapeutic modalities against AM.

SLUG is upregulated and induces epithelial mesenchymal transition in canine oral squamous cell carcinoma.

SLUG, encoded by the Snai2 gene, is known to play a role in epithelial-mesenchymal transition (EMT), which contributes to cell invasion and metastasis in some types of human carcinomas. However, the mechanisms and roles of EMT in canine squamous cell carcinoma (SCC) have not yet been elucidated. We have previously established canine oral SCC cell lines, including tonsillar SCC, and in this study, we evaluated the effects of SLUG on the phenotypes regarding EMT of canine SCC cells. First, immunohistochemical analysis revealed that SLUG is upregulated in canine oral SCC tissues compared to that in non-tumoural oral mucosa. Furthermore, gain-of-function and loss-of-function of SLUG revealed that SLUG partly contributed to migration and invasion of cells, as well as the upregulation of EMT markers such as vimentin and SNAIL. Thus, the current study suggests that SLUG promotes cell migration and invasion through EMT induction in canine oral SCC, as well as human cancers.

The Expression of Selected Wnt Pathway Members (FZD6, AXIN2 and β-Catenin) in Canine Oral Squamous Cell Carcinoma and Acanthomatous Ameloblastoma.

Simple SummaryThe expression patterns of selected Wnt pathway molecules were analyzed in two of the most common canine oral neoplasia—canine oral squamous cell carcinoma (COSCC) and canine acanthomatous ameloblastoma (CAA). We found an overlap of areas with high expression of FZD6 and SOX2 in COSCC, while cytokeratin expression was low in these areas, indicating the low differentiation status of these cells. In CAA, FZD6-positive areas expressed cytokeratin and exhibited features of squamous metaplasia. Moreover, the expression of β-catenin and AXIN2 was higher in both CAA and COSCC than in the healthy canine oral epithelium. This work uncovered the distinct expression patterns of Wnt molecules in both lesions, indicating the involvement of this pathway in the pathology of canine oral cancers, which presents opportunities for their usage for the prediction of cell behavior or in the development of new therapeutic approaches.The Wnt signaling pathway is well known to be involved in many types of human cancer; however, in veterinary medicine, the investigation of individual Wnt members’ expression, and their role in or association with oral tumor pathogenesis, is still underevaluated. We aim to determine the expression pattern of Frizzled-6 (FZD6) as one of the Wnt receptors in two of the most common canine oral neoplastic lesions—canine oral squamous cell carcinoma (COSCC) and canine acanthomatous ameloblastoma (CAA). While COSCC is a malignant tumor with aggressive biological behavior and a tendency to metastasize, CAA is a benign tumor with high local invasiveness. In CAA, the expression of FZD6 was mostly located in the center of the epithelial tumorous tissue, and cells exhibiting features of squamous metaplasia were strongly positive. In well-differentiated COSCC, FZD6 was expressed in the tumorous epithelium as well as the tumorous stroma. There was a negative correlation between cytokeratin expression and FZD6 expression in COSCC, where the central parts of the epithelial tumorous tissue were often FZD6-negative. The non-differentiated COSCC with low expression of cytokeratin exhibited a diffuse FZD6 signal. The invasive front with areas of tumor budding exhibited high FZD6 expression with a loss of cytokeratin expression. Moreover, the expression of β-catenin and AXIN2 was increased in comparison to gingiva. In conclusion, our study revealed significant differences in the expression patterns and the levels of FZD6 between COSCC and CAA, indicating the differential engagement of the Wnt pathway in these tumors.

A possible role of coarse fractionated radiotherapy in the management of gingival squamous cell carcinoma in dogs: A retrospective study of 21 cases from two referral centers in the UK.

Surgery with or without the addition of radiotherapy is the treatment of choice for canine oral squamous cell carcinoma (SCC). Fractionated radiotherapy alone is also effective in the long-term control of the disease, however coarse fractionated radiotherapy (CF-RT) for gingival SCC has not been extensively reported. The aim of this study was to describe side effects, clinical response, and median survival time (MST) of dogs with gingival SCC treated with CF-RT in the palliative and adjuvant setting. Twenty-one cases from two referral centres in the UK treated with CF-RT for gingival SCC between July 2013 and June 2019 were retrospectively evaluated. Of the 21 dogs, 11 developed mild acute adverse effects. Oral mucositis was the most common radiation induced toxicity. Three dogs developed chronic severe adverse effects (oro-nasal fistula, bone necrosis and gum recession). Overall clinical response rate was 77% in dogs receiving palliative treatment with MST of 365 days (60–1,095 days). MST was not reached for dogs treated in the adjuvant setting with a mean of 466 days (121–730 days). In cases of advanced gross disease CF-RT might have a role in short term palliation of clinical signs. However, it carries a significant risk of late toxicity for cases with unexpectedly long survival times and further investigations are required to identify an optimal CF-RT protocol. Randomized controlled trials are needed to confirm the role of CF-RT as adjuvant treatment of incompletely resected gingival SCC.